Exaggerated hypoxic pulmonary hypertension in endothelin B receptor-deficient rats

D. Dunbar Ivy, Masashi Yanagisawa, Cheryl E. Gariepy, Sarah A. Gebb, Kelley L. Colvin, Ivan F. McMurtry

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Mechanisms by which endothelin (ET)-1 mediates chronic pulmonary hypertension remain incompletely understood. Although activation of the ET type A (ETA) receptor causes vasoconstriction, stimulation of ET type B (ETB) receptors can elicit vasodilation or vasoconstriction. We hypothesized that the ETB receptor attenuates the development of hypoxic pulmonary hypertension and studied a genetic rat model of ETB receptor deficiency (transgenic sl/sl). After 3 wk of severe hypoxia, the transgenic sl/sl pulmonary vasculature lacked expression of mRNA for the ETB receptor and developed exaggerated pulmonary hypertension that was characterized by elevated pulmonary arterial pressure, diminished cardiac output, and increased total pulmonary resistance. Plasma ET-1 was five-fold higher in transgenic sl/sl rats than in transgenic controls. Although mRNA for prepro-ET-1 was not different, mRNA for ET-converting enzyme-1 was higher in transgenic sl/sl than in transgenic control lungs. Hypertensive lungs of sl/sl rats also produced less nitric oxide metabolites and 6-ketoprostaglandin F, a metabolite of prostacyclin, than transgenic controls. These findings suggest that the ETB receptor plays a protective role in the pulmonary hypertensive response to chronic hypoxia.

Original languageEnglish (US)
Pages (from-to)L703-L712
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume282
Issue number4 26-4
StatePublished - Jul 2 2002

Keywords

  • Endothelin receptors
  • Hypoxia
  • Nitric oxide
  • Prostacyclin
  • Pulmonary circulation

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Dunbar Ivy, D., Yanagisawa, M., Gariepy, C. E., Gebb, S. A., Colvin, K. L., & McMurtry, I. F. (2002). Exaggerated hypoxic pulmonary hypertension in endothelin B receptor-deficient rats. American Journal of Physiology - Lung Cellular and Molecular Physiology, 282(4 26-4), L703-L712.